Measuring Electrical Activity of the Brain: ERP Mapping in Alcohol Research.

The recording of brain electrical activity from scalp electrodes provides a noninvasive, sensitive measure of brain function. Event-related potentials (ERP's) are brain waves that are recorded while the subject is exposed to a specific sensory stimulus. Depending on experimental conditions, ERP's are useful in studying many brain functions, such as sensory and information processing (e.g., memory). The assessment of ERP's is useful in studying the effects of alcohol on brain function and in identifying people at risk for developing alcoholism. Computerized mapping techniques produce graphs or color-coded images to summarize data about the generation of ERP's in time and space.

R ecording brain electrical activity using mapping techniques, focusing on the ERP scalp electrodes provides noninva component P300. DAVID B. CHORLIAN, M.S., is a senior sive, sensitive measures of brain scientific programmer in the Neurody function (e.g., cognition). These electrical namics Laboratory, State University of recordings consist of two phenomena: the

RECORDING BRAIN
New York (SUNY) Health Science Center at Brooklyn, Brooklyn, New York. continuous electroencephalogram (EEG) ELECTRICAL ACTIVITY and timepointspecific eventrelated brain BERNICE PORJESZ, PH.D., is an assistant potentials (ERP's). Unlike positron emis The EEG is not linked in time to any spe professor in the Department of Psychiatry, sion tomography (PET) or magnetic reso cific event but instead reflects the activation SUNY Health Science Center at Brooklyn, nance imaging (MRI) techniques, brain level of various brain regions. For example, Brooklyn, New York. mapping does not construct an image of a a person in a relaxed state will manifest a hidden anatomical structure; rather, it illus great deal of simultaneous brain wave ac HOWARD L. COHEN, PH.D., is a research trates spatiotemporal brain activity (i.e., tivity occurring at a wave frequency between scientist in the Neurodynamics Laboratory, brain activity as it occurs in both space and 8 and 12 cycles per second. Conversely, SUNY Health Science Center at Brooklyn, time). This article presents a variety of brain ERP's represent brain electrical activity in Brooklyn, New York. response to specific sensory or cognitive events occurring at a specific time. In ad dition, ERP's consist of characteristic, highly reproducible wave forms that can be measured to within a fraction of a sec ond, providing an immediate record of the brain activity associated with information processing. Because ERP signals are small and are embedded in the ongoing EEG, statistical techniques are used to extract them from the background EEG. Depending on experimental conditions, ERP's may represent overlapping activity of many brain circuits. Therefore, they are useful in studying complex brain functions, such as sensory and information processing (e.g., memory). ERP's offer a unique ap proach for assessing brain function because they allow scientists to observe simultane ously electrical activity (i.e., electrophysi ology) and cognition.

How Are ERP's Obtained?
To record ERP's, subjects wear a cap em bedded with from 20 to 128 noninvasive scalp electrodes. ERP's can be measured in response to stimuli from any sensory modality (e.g., sight or sound) and also may be recorded while a behavioral task is being conducted. For example, ERP's can be obtained for visual stimuli using a method in which shapes or letters are presented on a computer screen while the subject performs a simple cognitive task, such as recognizing a particular shape. The subject may be asked to make a be havioral response (e.g., press a button whenever a particular shape appears) or keep count of how many specific stimuli have been presented. Scalp signals reflect ing brain electrical activity are recorded simultaneously from all electrodes as the subject processes the stimuli.

What Do ERP's Indicate?
The peaks (i.e., positive waves) and troughs (i.e., negative waves) of the ERP wave form, also known as positive and negative com ponents, are measured in microvolts (µV). These components are named according to their positive (P) or negative (N) polarity as well as their latency (i.e., the time of occur rence of the peak wave after the stimulus, measured in milliseconds [ms]). Thus, a negative ERP wave occurring 100 ms following the stimulus would be called the N1 or N100 wave. Early components (with a latency of less than 100 ms) are responses to the physical characteristics of the stimulus (e.g., intensity), whereas the later components are influenced by psychological factors (e.g., cognition).

What Is a P300?
Much attention has focused on the P300 component of the ERP, a prominent posi tive component peaking between 300 and 500 ms after a stimulus. Scalp recordings of P300 are strongest at the parietal area, a rear (i.e., posterior) brain region. The ERP task most commonly used to elicit the P300 is the socalled "oddball" task, in which subjects are asked to attend to and/or respond to a rare stimulus present ed in a series of other stimuli. For exam ple, in an auditory paradigm, the subject listens to frequent "boops" and rare "beeps" (targets) in a random stream of tone bursts presented about 1.5 seconds apart. The sub ject may be asked to press a button or count each time a target occurs (for a review, see Regan 1989). P300 results from auditory paradigms, however, are not as consistent as those from visual paradigms. Conse quently, the P300 data discussed here are from a study using a visual paradigm in which alcoholics, highrisk subjects, and control subjects pressed a button in response to the rare occurrence of the target letter "X" embedded in a sequence of other vis ual shapes.

Advantages of ERP Measurement in Alcoholism Research
ERP's provide sensitive measures of brain functions. Unlike other imaging techniques, ERP's reflect subtle, dynamic, realtime, millisecondtomillisecond transactions that are elicited while the brain is chal lenged and are therefore highly sensitive to specific brain processes. Most sensory activity occurs within 100 ms after a stim ulus is presented, and most cognitive ac tivity takes place within 500 ms. Although images obtained using PET also offer a functional measure of brain processes, elec trophysiological measures link images of brain activity to specific timepoints (i.e., provide a temporal resolution) with a pre cision far greater than that of PET's. Other imaging methods, such as MRI and com puted tomography (CT) scans, portray gross brain structure but do not reflect ongoing electrical activity. Thus, they cannot pro vide direct measures of brain function. ERP abnormalities, however, can be observed even when MRI and CT images reveal no anatomical changes. In addition, many EEG and ERP characteristics are extremely sen sitive to acute and chronic effects of alcohol on the brain and are responsive to intoxi cation, tolerance, withdrawal, and the ef fects of prolonged abstinence.
Electrophysiological features also may be hereditary markers of risk for alcoholism. Evidence indicates that the characteristics of both EEG's and ERP's are genetically determined and that P300 attributes gen erally differ between alcoholics and non alcoholics (Porjesz and Begleiter 1995). A recent twin study (O'Connor et al. 1994) reported that P300 amplitude is highly heri table; similar findings on the heritability of P300 are being obtained by researchers in the Collaborative Study on the Genetics of Alcoholism (COGA) through a large fam ily study (Porjesz et al. in press).

Amplitude and Latency Measures
Researchers have used various auditory and visual paradigms to study the P300 compo nent and have found the P300 amplitude to be smaller in alcoholics than in control sub jects (figure 1) (for a review, see Porjesz and Begleiter 1993). Researchers previously thought that these low P300 voltages re sulted from neurotoxic effects of alcohol on the brain. Low P300's, however, do not re cover with prolonged abstinence and can occur in subjects at risk for alcoholism prior to alcohol exposure. Thus, low P300 ampli tudes may characterize populations at risk for developing alcoholism (Polich et al. 1994).

Topographic Representations
Although amplitude and latency measures provide important information about brain function, they do not address the spatial dis tribution of ERP's across the scalp. Spatial distributions provide information about brain areas possibly involved in generating ERP activity. Displaying ERP's from multi ple electrodes does not show values across the entire scalp surface but only at the sites of the electrodes. Mathematical techniques enable researchers to assign values to the points that have not been directly meas ured; maps can then be created by calcu lating the values between electrode points. Figures 2 and 3 show two types of mapsspatiotemporal and topographic-based on this approach (Fein et al. 1992).
Topographic maps are frozen at a sin gle point in time, thereby losing the dy namic aspect of the recorded data. With the advent of computer technology, these spatial maps can be presented as a series of rapidly changing, computergenerated animations that describe how the topo graphic distribution of the recorded activity changes over time.

MAPPING OF CURRENT SOURCE DENSITY
Because voltages measured at a point on the scalp result from both local (i.e., di rectly under the electrode) and remote sources by mathematically transforming the ERP data, researchers can emphasize local sources. The data transformation produces a quantity known as the current source density (CSD), which represents the radially oriented current density at a point on the scalp. The CSD values de note current sources and "sinks" (i.e., locations where the current becomes un detectable). Researchers create CSD maps by taking simultaneous data from all the electrodes and converting them into spatial data. A CSD topographic map or spatio temporal map (figures 4 and 5) may dis play results in a more useful fashion than a topographic map based on ERP's (figures 2 and 3).
In the P300 experiment mentioned earlier, for example, the peak of the P300 component (occurring at 430 ms) from 61 scalp electrodes is transformed to CSD. In healthy control subjects, these maps indi cate both a large posterior focus of activity as well as front (i.e., anterior) foci (figure 4). These brainmapping techniques aid in pinpointing possible sites of brain dysfunc tion in alcoholics and in subjects at risk for developing alcoholism.
A comparison of CSD maps obtained from alcoholics and nonalcoholics shows weaker activity in the alcoholics' brains. Figure 5 displays the distribution of P300 activity across the alcoholics' scalps. Com pared with control subjects, alcoholics can appear to have a weaker posterior focus of activity and no clear frontal focus. There fore, control subjects and alcoholics ex hibit not only differences in amplitude but differences in spatial distributions, particularly in the brain's frontal regions.
A more elaborate analysis of the elec trophysiological data measures informa tion communication from one location in the cerebral cortex to another. If a tempo ral pattern of electrical activity at one electrode matches the pattern at another electrode a few milliseconds later, infor mation is likely being transferred from the first to the second location. Gevins and colleagues (1990) developed a mathemati cal method of examining timelagged CSD data while a subject simultaneously performs a task. The results are interpret ed as reflecting the activity of active networks in the cerebral cortex and can be applied to various ERP paradigms.

Structural Findings
To determine the relationship between brain structure and function, researchers have investigated the neuroanatomical origins of P300 using various techniques. Evidence from recordings obtained from electrodes implanted in the human brain implicates both the medial temporal lobe 1 as well as source(s) within the frontal lobe as contributing to P300 generation. These findings, coupled with the rather small ef fect that temporal lobe removal has on scalp P300 during auditory oddball tasks, sug gest that multiple brain sites contribute to the P300 (for a review, see Regan 1989).
Researchers have used noninvasive imaging techniques to assess brain struc ture. In a recent study using P300 ampli tude and MRI, Ford and colleagues (1994) reported that reduced P300's recorded dur ing both automatic and effortful attention tasks (i.e., tasks requiring subjects to focus intently) correlated with frontal and pari etal graymatter volumes. These findings are consistent with the CSD maps of P300 described earlier in which both parietal and frontal foci of activity were found. The re duced P300 amplitudes in alcoholics and their CSD maps may be manifestations of frontal lobe damage (see OscarBerman and Hutner 1993).
1 For a definition of this and other technical terms used in this article, see central glossary, pp. 293-295.

CONCLUSIONS
Electrophysiological recordings of ERP's reflect the activation of neural circuits in volved in the mediation of sensory and cog nitive processes. The assessment of ERP's has proven extremely useful in studying the effects of alcohol(ism) on brain func tion and in identifying people at risk for developing alcoholism. In contrast, con ventional imaging techniques have helped identify brain structural changes resulting from alcoholism. Electrophysiological brain mapping is the representation of brain func tioning in its spatiotemporal dimensions. These electrophysiological techniques pro vide exquisite temporal resolution of brain processes and have now been enhanced to provide spatial information about possible brain generators of this activity. These novel techniques not only potentially pro vide a window into the brain's function but also may contribute simple clinical tools for identifying both the adverse effects of alcohol consumption on the brain and peo ple who may be at risk for alcoholism.